The proposed work will investigate the semi-permanent increases in the strength of synaptic connections which occur in the hippocampus following brief trains of repetitive stimulation of those connections. Three lines of investigation will be conducted: 1) What are the mechanisms responsible for the induction and maintenance of the long-term potentiation effect (LTP) produced by repetitive stimulation? Amongst other ideas, the proposed work will examine the hypotheses that influxes of calcium trigger LTP, that changes in a particular phosphoprotein represent an intermediate step in its production, and that ultra-structural changes represent the final substrates of the effect; 2) Is there a process which acts in an opposite direction to potentiation to produce long term decreases in synaptic strength? These experiments will expand on findings which suggest that repetitive low frequency stimulation can reverse the long-term potentiation. For the most part the first two groups of studies will use the in vitro hippocampal slice preparation. 3) Do changes occur in specific synaptic systems in hippocampus during learning and if so do these changes represent the operation of processes which are responsible for phenomena like long-term potentiation? This last group of experiments will make use of a "chronic" rat preparation.